JH8, A GENE HIGHLY HOMOLOGOUS TO THE MOUSE JERKY GENE, MAPS TO THE REGION FOR CHILDHOOD ABSENCE EPILEPSY ON 8Q24

Insertional inactivation of the jerky gene in transgenic mice resulted epileptic seizures, suggesting that the jerky gene was responsible fo r mouse epilepsy. To isolate a human homologue of the jerky gene, we s creened an Expressed Sequence Tag (EST) database using the cDNA sequen ce of the mouse jerky gene and identified several EST clones which con tained homologous sequences to mouse jerky gene. Using a clone which s howed highest homology as a probe, we isolated cDNA clones from a huma n fetal brain cDNA library. Sequence analysis of these clones named JH 8 (jerky homologue of Human on chromosome 8) indicated that it encoded a putative protein with 520 amino acid residues. The JH8 gene has 77% identity to the mouse jerky gene at the DNA level, and its protein ha s 76% identity and 84% similarity to the mouse protein at the amino ac id level. Northern blot analysis showed that the JH8 gene is expressed ubiquitously with a major transcript of about 9.5 kb in size, Fluores cence in situ Hybridization (FISH) analysis and radiation hybrid panel mapping revealed that the JH8 gene was located on chromosome band 8q2 4.3 in a region that was syntenic to mouse chromosome 15, the mapping site of the mouse jerky gene. Childhood Absence Epilepsy (CAE), one ty pe of Idiopathic Generalized Epilepsy (IGE), has been mapped to chromo some 8q24,3 by linkage analysis. These results suggest that JH8 is a s trong candidate gene for CAE. (C) 1998 Academic Press.